Ethical Issues When Considering Liver Donor Versus Deceased Donor Liver Transplantation

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Abbreviations

ALF

acute liver failure

DDLT

deceased donor liver transplant

HCC

hepatocellular carcinoma

HIPAA

Health Insurance Portability and Accountability Act of 1996

LDLT

living donor liver transplant

LT

liver transplantation

MELD

Model for End‐Stage Liver Disease

UCSF

University of California, San Francisco

Deceased donors remain the primary source of organs for patients wait‐listed for liver transplantation (LT). In 2019, 8372 deceased donor liver transplants (DDLTs) were performed, compared with 524 living donor liver transplants (LDLTs) (Fig. 1). ¹ The number of LDLTs has not significantly increased over time in the United States because of local surgical expertise, programmatic decisions, and risks to healthy living donors. ² Given the organ shortage, the patient and the transplant team may opt to pursue LDLT over DDLT. This practice raises several concerns regarding the ethical soundness of LDLT. Our group’s review in LT discusses various ethical concerns based on actual cases, as well as potential approaches to optimize the informed consent process. ³

FIG 1.

Number of transplant cases in the United States per year classified by donor type. Note the large number of DDLTs compared with LDLTs. *Numbers updated as of January 31, 2020. Source: Organ Procurement and Transplantation Network, https://optn.transplant.hrsa.gov/.

Ethical Dilemmas

LDLT may become an option for patients who are ineligible for or unlikely to receive DDLT (Table 1). Although the benefit of DDLT is clear, LDLT presents ethical challenges regarding honoring principles of medical ethics, including autonomy, nonmaleficence, and beneficence, among others (Table 2). The transplant team must balance the patient’s mortality without transplantation and the serious medical risks to the healthy living donor versus the potential lifesaving benefits to the patient and the lack of any direct medical benefit to the donor. Organ Procurement and Transplant Network Policy 14.3 outlines informed consent requirements for living donors. ⁴

TABLE 1.

Possible Indications for LDLT

Low MELD (not reflecting severity of illness)

Cholestatic liver disease/recurrent cholangitis

Severe encephalopathy

Refractory ascites

Cachexia

HCC outside tumor criteria

Patients in regions with long wait times

Patients declined from DDLT

Active alcohol use

TABLE 2.

Considering Principles of Medical Ethics in LDLT Scenarios

Autonomy	Does the donor have enough information regarding the circumstances of living donation to provide adequate informed consent?
	How can we provide adequate details without violating HIPAA?
	Do people have a "right to donate"? What limitations do physicians have in making judgments on a donor’s behalf?
Nonmaleficence	How do transplant teams honor the principle of "do no harm" knowing that living donors assume medical risk without any direct medical benefit?
	How can transplant teams minimize risks to the donor, including medical and psychosocial complications?
Utility	Given that LDLT increases the total number of available transplant organs, should LDLT be encouraged, even with potentially inferior recipient outcomes?
Beneficence	What are the donor’s motives for proceeding with an LDLT?
	How do transplant teams ensure that recipient outcomes are optimized?
Equity	Should “social worth” criteria be factored into the organ allocation system, thus necessitating LDLT consideration?

Several factors make informed consent problematic. Questions may arise regarding adequate disclosure of information to donors, donor comprehension of information, and donor voluntariness. ⁵ Donors may not adequately appreciate the morbidity and mortality associated with surgery, along with long‐term psychosocial impact. Abecassis et al. ⁶ and the A2ALL (Adult‐to‐Adult Living Donor Liver Transplant Cohort Study) Study Group previously reported an overall donor mortality rate of 0.4%, with complications occurring in 40% of donors. Moreover, donors may be under internal and external pressure to donate given the severity of their loved one’s illness and the high risk for mortality without transplantation. ⁷ Following is a summary of the issues discussed in the companion article.

Alcoholic Hepatitis

Most patients with alcoholic hepatitis are excluded from DDLT primarily because the high risk for relapse after transplantation outweighs the public health consideration of diverting a deceased donor liver away from candidates with non‐alcohol‐related liver diseases. However, in the setting of LDLT, ethical analysis must consider both the risks to recipients from not receiving lifesaving treatment and the risks to the live liver donor, regardless of the patients’ alcohol use.

Given live liver donors’ high morbidity and mortality, donors must seriously weigh the risks and benefits of transplant to themselves and the recipient. Potential donors may desire information about the recipient’s disease, disease etiology, and risk for relapse in LT recipients to help inform their decision making. Yet HIPAA (Health Insurance Portability and Accountability Act of 1996) protects recipient confidentiality, which may undermine donor comprehension of the recipient’s liver disease. ⁵ A compromise must be reached that respects recipient privacy and donor autonomy.

Acute Liver Failure

Emergent LT is central to the treatment of acute liver failure (ALF), as spontaneous recovery occurs in 10%‐40% of patients, whereas survival rates after LT are greater than 80%. ⁸ Although patients with ALF receive the highest priority for DDLT, the mortality rate during the waiting period is exceedingly high, thus leading to consideration of LDLT. ⁸ , ⁹ Given time constraints in an emergent situation, the living donor may attain only a limited understanding of the risks, benefits, alternatives, and procedures for the donor and recipient, thus jeopardizing a donor’s ability to make an informed decision. This dilemma is pronounced in cases of distant donor‐recipient relationships, which merit careful attention to donor motivation and the potential psychosocial benefits the donors gain by donating. Although donors do not receive any medical benefit and expose themselves to harm, research suggests consideration of “nonhealthy benefits.” ¹⁰ For example, many donors cite increased self‐esteem and satisfaction in helping others as factors influencing their decision to donate. Furthermore, declining a donor may place that person at risk for losing a loved one and/or increased caregiver burdens. ¹⁰

Lastly, because potential recipients with ALF commonly lack decision‐making capacity, ethical issues may arise regarding surrogate decision‐makers and their ability to honor the patient’s treatment preferences.

Hepatocellular Carcinoma

How should patients who fall outside of the Milan criteria for DDLT pursue a transplant?

Patients transplanted with these criteria have low recurrence and excellent survival rates posttransplant. ¹¹ Nevertheless, the Milan criteria have been criticized for being overly restrictive, especially in patients with large lesions. The University of California, San Francisco (UCSF) developed broader criteria (Table 3), which document improvement in patient outcomes without increases in mortality or disease recurrence rates. ¹²

TABLE 3.

Comparison of Criteria to Identify Best Candidates for Orthotopic LT in Patients With HCC

Milan criteria 11

Single lesion ≤5 cm or fewer than 3 nodules each ≤3 cm

Without vascular or extrahepatic invasion

UCSF criteria 12

Single lesion ≤6.5 cm or fewer than 3 nodules with the largest tumor ≤4.5 cm and total tumor diameter ≤8 cm

Without vascular or extrahepatic invasion

In certain scenarios, LDLT is considered for patients who fall outside of these criteria.

Research suggests that LDLT may have similar outcomes in patients outside the Milan criteria, although the risk for hepatocellular carcinoma (HCC) recurrence is higher. ¹³ No consensus exists about acceptable HCC recurrence risk. Although recurrence rates remain high, transplantation may provide better survival in select patients than denying transplantation. The recipient, transplant team, and potential donor must all determine their willingness to accept the higher risks for posttransplant HCC recurrence given the risks to donors. ¹⁴ , ¹⁵ Furthermore, in cases of predicted poor posttransplant prognosis, providers must consider a cutoff point where the risks of transplantation outweigh the benefits to the recipient and donor. This line must be individualized for each case based on tumor biology, imaging findings, and laboratory markers. ¹⁶ , ¹⁷

Recommendations

Central to these ethical dilemmas is the concept of informed consent. Because no guidelines exist to navigate this process in these situations, we recommend open communication between both parties, while ensuring that donors are protected against undue pressure that may arise. Recipients should be aware of risks and benefits to donors associated with LDLT and the risk for HCC recurrence. Donors should be informed about the recipient’s underlying disease, risk for relapse, and potential complications to the graft, per recipient consent to disclose such information. In cases characterized by time constraints, early ethics consultation and psychological evaluations may be helpful. Interventions to improve donor‐clinician communication, such as use of comprehension assessment and e‐health educational tools, may help convey risks. A separate donor evaluation team can be used to minimize threats to donor voluntariness and transplant team conflicts of interest. Further research should be conducted regarding the minimum information required for informed consent in the earlier situations, and establish an efficient process to obtain informed consent in urgent situations.

Conclusion

LDLT requires detailed discussions between donor, recipient, and transplant team regarding risks and benefits. Open communication augments donor understanding of potential complications. Through greater attention to informed consent, the liver transplant community can foster greater satisfaction with LDLT.